The carbapenem compounds which have been developed and commercialized are poor in absorbability from the digestive tract and therefore, they are clinically used only in the form of injections, mainly intravenous injections. However, in the clinical field, it is desirable to select several administration routes from the viewpoint of circumstances or wishes of a patient, a therapeutic object, etc. Especially, oral administration of an antibacterial agent is easy and convenient for administration to a patient in comparison with injection. In view of the care of a patient at home, oral administration of the antibacterial agent is more convenient and the clinical usability is extremely high. It has been strongly desired in the clinical field to develop a carbapenem compound which is rich in safety, is orally administrable and has a potent antibacterial activity, especially against penicillin resistant Streptococcus pneumoniae (PRSP) or Haemophilus influenzae (which widely gain resistance to known β-lactam agents by mutation of a penicillin binding protein (PBP), such as β-lactamase non-producing ampicillin resistant Haemophilus influenzae (BLNAR) which have been recently increasingly isolated and provide a clinical trouble.). However none of such agents has been put on the market. Tricyclic carbapenem compounds which have been studied and developed until now are disclosed for example, in WO92/03437. These compounds have a characteristic structure in a side chain having a ring which is fused via C—C bond and they are modified to a prodrug thereof for increase of oral absorbability, but their safety in the clinical test is not reported. Besides, there are several known 1β methylcarbapenem compounds (see WO 92/03437, Japanese patent publication A 2-49783, Japanese patent publication A 8-53453, WO 98/34936, WO 99/57121, Japanese patent publication A 4-279588, Japanese patent publication A 2-223587, and Antimicrobial Agents and Chemotherapy, March 1999, p 460-464). All of them have a structural property having 1β-methyl group and a side chain via sulfide bond which are said to contribute to an increase of chemical stability and in vivo (biological) stability, and are modified to a prodrug of them for increase of oral absorbability. Especially, the clinical trial was carried out on compounds disclosed in Japanese patent publication A 2-49783 and Japanese patent publication A 8-53453, but the safety of them and so on have been not clear.
On the other hand, carbapenem compounds having an aryl ring via C—C bond as a side chain structure were known since 1980s (see U.S. Pat. Nos. 4,543,257, 4,775,669, 5,258,509, WO 02/053566, Tetrahedron, 1983, Vol. 39, p 2531-2549, Journal of Medicinal Chemistry, 1987, Vol. 30, p 871-880, EP 538001, and EP 538016). For example, in U.S. Pat. No. 4,543,257, carbapenam compounds directly substituted by para-methoxyphenyl group at position 3 of 7-oxo-1-azabicyclo[3.2.0]hept-2-ene which is a core structure of the carbapenem, and various compounds are described, and in the Journal of Medicinal Chemistry, Vol. 30, p 871-880 (1987), carbapenam compounds directly substituted by para-methoxyphenyl group at position 3 of 7-oxo-1-azabicyclo[3.2.0]hept-2-ene which is a basic nucleus of the carbapenem and so on are described. Although there are many other reports on these compounds, these reports are concerned only to studies and developments on injections thereof, but not to studies for oral application thereof.
Recently, carbapenem derivatives having a benzene ring and so on directly bound by substituted carbamoyl group at position 3 of 7-oxo-1-azabicyclo[3.2.0]hept-2-ene which is a core structure of the carbapenem (for example, WO 02/053566), carbapenem derivatives having a benzene ring bound via spacer with substituted carbamoyl group at position 3 of 7-oxo-1-azabicyclo[3.2.0]hept-2-ene which is a core structure of the carbapenem (for example, WO 03/040146), and carbapenem derivatives having a substituted pyridine ring, etc. at position 3 of 7-oxo-1-azabicyclo[3.2.0]hept-2-ene which is a core structure of the carbapenem (for example, WO 03/089431) are suggested to be used for oral agents, but the carbapenem derivatives having such a substituent pattern as the compound of the present invention are not known and that such compounds are not known as oral antibacterial agents.